Terradas Mariona, Capellá Gabriel, Valle Laura
Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, Hospitalet de Llobregat, 08908 Barcelona, Spain.
Program in Molecular Mechanisms and Experimental Therapy in Oncology (Oncobell), IDIBELL, Hospitalet de Llobregat, 08908 Barcelona, Spain.
J Clin Med. 2020 Jun 23;9(6):1954. doi: 10.3390/jcm9061954.
In the past two decades, multiple studies have been undertaken to elucidate the genetic cause of the predisposition to mismatch repair (MMR)-proficient nonpolyposis colorectal cancer (CRC). Here, we present the proposed candidate genes according to their involvement in specific pathways considered relevant in hereditary CRC and/or colorectal carcinogenesis. To date, only pathogenic variants in may be convincedly linked to hereditary CRC. Nevertheless, accumulated evidence supports the involvement in the CRC predisposition of other genes, including , , , , , , , , or the epigenetic alteration of . The contribution of the identified candidate genes to familial/early onset MMR-proficient nonpolyposis CRC, if any, is extremely small, suggesting that other factors, such as the accumulation of low risk CRC alleles, shared environmental exposures, and/or gene-environmental interactions, may explain the missing heritability in CRC.
在过去二十年中，已经开展了多项研究以阐明错配修复（MMR）功能正常的非息肉病性结直肠癌（CRC）易感性的遗传原因。在此，我们根据其参与遗传性CRC和/或结直肠癌发生中被认为相关的特定途径，提出候选基因。迄今为止，只有 中的致病变异可被确凿地与遗传性CRC联系起来。然而，积累的证据支持其他基因参与CRC易感性，包括 、 、 、 、 、 、 、 或 的表观遗传改变。已鉴定的候选基因对家族性/早发性MMR功能正常的非息肉病性CRC的贡献（如果有的话）极小，这表明其他因素，如低风险CRC等位基因的积累、共同的环境暴露和/或基因-环境相互作用，可能解释了CRC中缺失的遗传度。
